Research

Clinical Studies at the Diabetes and Obesity Center

In partnership with the dedicated physicians at UofL, the Diabetes and Obesity Center supports clinical studies to translate discoveries in basic science and to contribute to the development of new therapeutic strategies for the prevention and treatment of diabetes, obesity and cardiovascular disease.

In 2008, the Center began working with disadvantaged and underserved communities in order to assess the impact of environmental factors on diabetes and heart disease. With help from UofL’s Preventive Cardiology Clinic, the Louisville Healthy Heart Project collects data on environmental factors that influence the prevalence and the severity of heart disease . Patients receiving care at UofL’s Preventive Cardiology Clinic are offered the opportunity to participate in investigator-initiated research studies that examine the effects of environmental pollutants on endothelial progenitor cells. The Project also provides outstanding opportunities for research and training in the fields of preventive cardiology, cardiovascular epidemiology and environmental cardiology.

PI: Timothy O’Toole
Co-Investigator: Sathya Krishnasamy
The REVIVE (Role of EPCs and Vascular Progenitors In Vascular Endothelial Health) study, recently launched in collaboration with the Division of Endocrinology, explores whether diabetes causes a decrease in circulating endothelial progenitor cells, diminishing their ability to promote angiogenesis. This project is a case-controlled study of 50 diabetic, 50 pre-diabetic and 50 non-diabetic subjects recruited from the UofL Diabetes Clinic.

PI: Aruni Bhatnagar
Co-Investigator: Jorge Rodriguez
The OSIRIS (Obesity and Stem cell-Induced Regeneration In Systemic vascular disease) study, in collaboration with the Department of Surgery, examines the effects of bariatric surgery on insulin resistance and stem cell function in the morbidly obese. The overall aim of OSIRIS is to develop a better understanding of how bariatric surgery alters systemic inflammation and the lipid-mediators of resolution, such as resolvins. Patients are enrolled before surgery and followed for 3 years.


Basic Research Projects at the Diabetes and Obesity Center

Diabetes mellitus and associated hyperglycemia leads to elevation of calcium in vascular smooth muscle, contributing to the development of cardiovascular complications. Our work has discovered altered mechanisms of membrane excitability and direct stimulation of Ca2+-permeable ion channels that may act in concert in diabetic patients to enhance vasoconstriction, ultimately limiting blood flow and raising vascular resistance..

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Exposure to ambient air pollution is one of the leading causes of death world-wide. Many studies have shown that exposure to ambient fine particulate matter (PM2.5) increases the risk of cardiovascular disease (CVD), type 2 diabetes (T2D) and cardiovascular mortality in susceptible individuals. Nevertheless, the pathophysiology underlying these effects remains elusive.

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Our recent work has uncovered that nutrient excess delays resolution of acute inflammation. Importantly, promoting resolution with pro-resolving lipid mediators restores insulin sensitivity and enhances diabetic wound healing. Completion of this project will help identify cellular mechanisms that propagate chronic unresolved adipose tissue inflammation in obesity and diabetes, providing new therapeutic targets for the treatment of T2D.

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The mechanisms by which diabetes increases heart failure severity remain poorly understood. Although several processes (such as severity of stenosis, duration of ischemia) contribute to the severity of ischemic injury, recent evidence suggests that infiltration of inflammatory cells plays a critical role not only as a determinant of tissue injury but also in promoting scar formation and infarct healing.

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Acute myocardial infarction (MI) remains a leading cause of death worldwide. It is most commonly caused by thrombi overlying disrupted atherosclerotic plaques. However, while plaque disruption often precipitates thrombosis, autopsy studies have shown that plaque rupture alone is not sufficient to cause an occlusive coronary thrombus resulting in acute MI. As many as 79% of plaque ruptures do not result in occlusive coronary thrombosis.

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